Semaphorin 3A-Glycosaminoglycans Interaction as Therapeutic Target for Axonal Regeneration.

Semaphorin 3A (Sema3A) is a cell-secreted protein that participates in the axonal guidance pathways. Sema3A acts as a canonical repulsive axon guidance molecule, inhibiting CNS regenerative axonal growth and propagation. Therefore, interfering with Sema3A signaling is proposed as a therapeutic target for achieving functional recovery after CNS injuries.

Dynamic Covalent Identification of an Efficient Heparin Ligand.

Despite heparin being the most widely used macromolecular drug, the design of small-molecule ligands to modulate its effects has been hampered by the structural properties of this polyanionic polysaccharide. Now a dynamic covalent selection approach is used to identify a new ligand for heparin, assembled from extremely simple building blocks. The amplified molecule strongly binds to heparin (K in the low μm range, ITC) by a combination of electrostatic, hydrogen bonding, and CH-π interactions as shown by NMR and molecular modeling.

Regioselective Synthesis of a Family of β-Lactams Bearing a Triazole Moiety as Potential Apoptosis Inhibitors.

Apoptosis is a biological process important to several human diseases; it is strongly regulated through protein-protein interactions and complex formation. We previously reported the synthesis of apoptosis inhibitors bearing an exocyclic triazole amide isoster by using an Ugi four-component coupling reaction (Ugi-4CC), followed by a base-promoted intramolecular cyclization. Depending on the substitution patterns and the reaction conditions, this cyclization forms the six- or four-membered ring.

Cationic Peptides and Peptidomimetics Bind Glycosaminoglycans as Potential Sema3A Pathway Inhibitors.

Semaphorin3A (Sema3A) is a vertebrate-secreted protein that was initially characterized as a repulsive-guidance cue. Semaphorins have crucial roles in several diseases; therefore, the development of Sema3A inhibitors is of therapeutic interest. Sema3A interacts with glycosaminoglycans (GAGs), presumably through its C-terminal basic region.

Efficient Synthesis of Conformationally Restricted Apoptosis Inhibitors Bearing a Triazole Moiety.

Apoptosis is a biological process relevant to different human diseases that is regulated through protein-protein interactions and complex formation. Peptidomimetic compounds based on linear peptoids and cyclic analogues with different ring sizes have been previously reported as potent apoptotic inhibitors. Among them, the presence of cis/trans conformers of an exocyclic tertiary amide bond in slow exchange has been characterized.

15N NMR spectroscopic and theoretical GIAO-DFT studies for the unambiguous characterization of disubstituted 1,2,3-triazoles.

The 1,2,3-triazole ring has recently attracted a renewed interest as a structural scaffold with many applications in different fields. However, very often, the unambiguous assignment of the correct structure is not an easy task, and the development of robust characterization methodologies is needed. Herein, the three possible isomeric forms of disubstituted 1,2,3-triazole (1,4- or 1,5- or 2,4-disubstituted derivatives) have been characterized and distinguished by routine (1)H/(15)N gHMBC experiments at (15)N natural abundance.

Optimizing the control of apoptosis by amide/triazole isosteric substitution in a constrained peptoid.

Apoptosis is a biological process relevant to several human diseases that is strongly regulated through protein-protein complex formation. We have previously reported a peptidomimetic compound as potent apoptotic modulator. Structural studies of this compound showed the presence of cis/trans isomers of the exocyclic tertiary amide bond in slow exchange.